Abstract
BackgroundTrimethylation of histone H3 on lysine 9 (H3K9me3) at satellite DNA sequences has been primarily studied at (peri)centromeric regions, where its level shows differences associated with various processes such as development and malignant transformation. However, the dynamics of H3K9me3 at distal satellite DNA repeats has not been thoroughly investigated.ResultsWe exploit the sets of publicly available data derived from chromatin immunoprecipitation combined with massively parallel DNA sequencing (ChIP-Seq), produced by the The Encyclopedia of DNA Elements (ENCODE) project, to analyze H3K9me3 at assembled satellite DNA repeats in genomes of human cell lines and during mouse fetal development. We show that annotated satellite elements are generally enriched for H3K9me3, but its level in cancer cell lines is on average lower than in normal cell lines. We find 407 satellite DNA instances with differential H3K9me3 enrichment between cancer and normal cells including a large 115-kb cluster of GSATII elements on chromosome 12. Differentially enriched regions are not limited to satellite DNA instances, but instead encompass a wider region of flanking sequences. We found no correlation between the levels of H3K9me3 and noncoding RNA at corresponding satellite DNA loci. The analysis of data derived from multiple tissues identified 864 instances of satellite DNA sequences in the mouse reference genome that are differentially enriched between fetal developmental stages.ConclusionsOur study reveals significant differences in H3K9me3 level at a subset of satellite repeats between biological states and as such contributes to understanding of the role of satellite DNA repeats in epigenetic regulation during development and carcinogenesis.
Highlights
Trimethylation of histone H3 on lysine 9 (H3K9me3) at satellite DNA sequences has been primarily studied atcentromeric regions, where its level shows differences associated with various processes such as development and malignant transformation
We identified annotated satellite DNA instances that overlapped the coordinates of problematic regions compiled by the Encyclopedia of DNA Elements (ENCODE) project [27], which we refer to as the blocklist throughout the manuscript [36, 37]
The results suggest that the H3K9me3 signal at satellite elements that did not intersect any component on the blocklist is less likely influenced by ambiguously mapped reads
Summary
Trimethylation of histone H3 on lysine 9 (H3K9me3) at satellite DNA sequences has been primarily studied at (peri)centromeric regions, where its level shows differences associated with various processes such as development and malignant transformation. Martens et al [20] found that epigenetic modifications at interspersed repeats such as TEs vary in chromatin of distinct cell types and proposed that these elements may play a role during lineage specification as well as in conversion to neoplastic or senescent state. They found that across the same sample set, the H3K9me is stable at tandem satellite repeats. There are no data regarding potential change and dynamics of H3K9me level at interspersed satellite elements located outside of pericentromeric regions during development as well as in cancer cells
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